Minimally invasive method for the point-of-care quantification of lymphatic vessel function

JCI Insight. 2019 Feb 21;4(4):e126515. doi: 10.1172/jci.insight.126515.

Abstract

Current clinical methods for the evaluation of lymphatic vessel function, crucial for early diagnosis and evaluation of treatment response of several pathological conditions, in particular of postsurgical lymphedema, are based on complex and mainly qualitative imaging techniques. To address this unmet medical need, we established a simple strategy for the painless and quantitative assessment of cutaneous lymphatic function. We prepared a lymphatic-specific tracer formulation, consisting of the clinically approved near-infrared fluorescent dye, indocyanine green, and the solubilizing surfactant Kolliphor HS15. The tracer was noninvasively delivered to the dermal layer of the skin using MicronJet600 hollow microneedles, and the fluorescence signal decay at the injection site was measured over time using a custom-made, portable detection device. The decay rate of fluorescence signal in the skin was used as a direct measure of lymphatic vessel drainage function. With this method, we could quantify impaired lymphatic clearance in transgenic mice lacking dermal lymphatics and distinguish distinct lymphatic clearance patterns in pigs in different body locations and under manual stimulus. Overall, this method has the potential for becoming a noninvasive and quantitative clinical "office test" for lymphatic function assessment.

Keywords: Dermatology; Diagnostic imaging; Lymph; Vascular Biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Area Under Curve
  • Female
  • Fluorescent Dyes / administration & dosage*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics
  • Humans
  • Indocyanine Green / administration & dosage
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacokinetics
  • Lymphatic Vessels / diagnostic imaging*
  • Lymphatic Vessels / physiopathology
  • Lymphedema / diagnosis*
  • Lymphedema / physiopathology
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Needles
  • Point-of-Care Systems*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Skin / diagnostic imaging*
  • Stearates / administration & dosage
  • Stearates / chemistry
  • Swine

Substances

  • Fluorescent Dyes
  • Kolliphor HS 15
  • Stearates
  • Polyethylene Glycols
  • Indocyanine Green